Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate recognition.
ApoB RNA-editing enzyme (APOBEC-1) is a cytidine deaminase. Molecular modeling and mutagenesis show that APOBEC-1 is related in quaternary and tertiary structure to Escherichia coli cytidine deaminase (ECCDA). Both enzymes form a homodimer with composite active sites constructed with contributions from each monomer. Significant gaps are present in the APOBEC-1 sequence, compared to ECCDA. The combined mass of the gaps (10 kDa) matches that for the minimal RNA substrate. Their location in ECCDA suggests how APOBEC-1 can be reshaped to accommodate an RNA substrate. In this model, the asymmetrical binding to one active site of a downstream U (equivalent to the deamination product) helps target the other active site for deamination of the upstream C substrate.
Navaratnam
N
N
MRC Molecular Medicine Group, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Fujino
T
T
Bayliss
J
J
Jarmuz
A
A
How
A
A
Richardson
N
N
Somasekaram
A
A
Bhattacharya
S
S
Carter
C
C
Scott
J
J
D000071479:APOBEC-1 Deaminase; D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017393:RNA Editing; D012329:RNA, Bacterial / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D001055:Apolipoproteins B; D012329:RNA, Bacterial; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; D003564:Cytidine Deaminase